We offer 13 individual fully funded research projects in our network
Looking for new talents
Position 1
Erasmus MC, NL
Biochemistry of DNA mismatch repair: Function of the MutS and MutSα state machine
filled
Position 2
University of Bristol, UK
Symmetry and Asymmetry in Nucleotide Excision Repair of DNA
filled
Position 3
Justus Liebig University, DE
Function of the MutL state machine
filled
Position 4
Leiden University Medical Center, NL
Unraveling the organization of the mismatch strand removal process
filled
Position 5
Netherlands Cancer Institute, NL
Structure and Function of the MutSα and MutLα state machines
available
Position 6
University of Bristol, UK
Non-canonical roles for UvrD in DNA repair
filled
Position 7
University of Leeds, UK
Structural mass spectrometry for the analysis of nucleic-acid:protein interactions and applications in the study of DNA repair complexes
filled
Position 8
French National Centre for Scientific Research, FR
Single-molecule characterization of transcription-coupled DNA repair
filled
Position 9
French National Centre for Scientific Research, FR
Single-molecule characterization of DNA mismatch repair
filled
Position 10
Erasmus MC, NL
Biochemistry of DNA mismatch repair: Coordination of DNA mismatch repair by multiple state machines
filled
Position 11
University of Central Finland, FI
Structural mass spectrometry for the analysis of protein:protein complex formation and conformational changes in DNA repair proteins
filled
Position 12
Chalmers University of Technology, SE
Diffusion of MMR-proteins along nanoconfined DNA.
filled
Position 1: PhD Student at Erasmus MC, Rotterdam, the Netherlands
Biochemistry of DNA mismatch repair: Function of the MutS and MutSα state machine
In your studies you will aim to identify (1) at which reaction steps ATP hydrolysis by MutS/ MutSα is required, (2) how this controls protein-DNA and protein-protein complex formation, and (3) what is the role of ATPase asymmetry.
Job description
DNA mismatch repair is important for maintaining genome stability through repair of DNA replication errors. Non-functional mismatch repair results in a mutator phenotype and in humans increases the risk to develop cancer. Mismatch repair involves the coordinated action of multiple proteins, amongst which MutS (in prokaryotes) and MutSα (in eukaryotes) that recognize the replication error. This project will address the structural and functional consequences of ATP hydrolysis by the repair proteins MutS and MutSα for coordinating the timing, location and directionality of the DNA mismatch repair reaction. In your studies you will aim to identify (1) at which reaction steps ATP hydrolysis by MutS/ MutSα is required, (2) how this controls protein-DNA and protein-protein complex formation, and (3) what is the role of ATPase asymmetry. You will be trained in protein purification and characterization, protein crosslinking, FRET-based complex formation assays (with University of Giessen) and in vitro DNA repair assays to study the coordinated enzyme activities during DNA mismatch repair.
Work Environment
This position is part of the Doctoral Training Network RepState, a highly collaborative consortium consisting of 14 European participants coming from academia, industry and the creative sector. You will be immersed in an international, multidisciplinary training environment in fundamental life sciences and obtain insight into the role of basic chemical and physical principles underlying molecular steps in complex yet integrated molecular processes. As the research relies on cutting-edge technologies, development of new approaches will be an integral part of your project. Training includes one or more rotations within European partner laboratories. Through collaboration with industry, you will learn how technology development drives innovation in research. In addition, you will learn how to disseminate and communicate your project in close collaboration with the creative sector.
For this project you will be employed by Erasmus MC. This is the largest academic hospital in The Netherlands and strives towards a healthy population and excellence in healthcare through research and education. The Department of Molecular Genetics is well known within the field of DNA repair for its competitive international research which spans the experimental range from animal models to single molecule imaging. Our research group focuses on biochemical and enzymatic approaches to understand the mechanisms of complex genome transactions such as DNA mismatch repair and the regulation of homeologous recombination at the molecular level.
Qualifications and skills
We are looking for an enthusiastic candidate with a MSc in Biochemistry, Structural Biology or closely related field, good command of English (IELTS grade min. 6.5, or equivalent). We welcome applicants of all nationalities. Being able to present a certificate of good conduct is a condition for the appointment.
There are strict eligibility requirements for the PhD positions in MSCA-DN:
- Applicants should not have resided or performed their main activity (work, studies, etc) in the Netherlands for more than 12 months in the 3 year period immediately prior to the start date of this position.
- Applicants for the PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).
Terms of employment
You will receive a temporary position for 4 years. The gross monthly salary is € 2.789,-in the 1st year and increases to € 3.536,- in the 4th year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC). Additionally, employment terms for Marie Curie projects (https://marie-sklodowska-curie-actions.ec.europa.eu/ ) apply for the first three years of employment.
Information and Application
The position is filled
Position 2: PhD Student at University of Bristol, UK
Symmetry and Asymmetry in Nucleotide Excision Repair of DNA
This project will focus on the role of the dimeric UvrA ATPase in global and transcription-coupled nucleotide excision repair (NER)
Applications are invited for a fully-funded 3-year PhD studentship starting in Autumn 2023 as part of the EU-wide doctoral training network RepState.
PhD Project Description
RepState is a highly collaborative and innovative doctoral training network consisting of 14 participants from academia, industry and the creative sector. It will train a new generation of scientists in biochemistry and biophysics to address central questions in biology concerning the mode of action of critical DNA Repair proteins. If left unchecked, unrepaired damage pre-disposes us to cancer and developmental defects. Accordingly, inherited or somatic mutations in DNA repair proteins are strongly associated with human disease including cancer. Moreover, DNA repair pathways are drug targets because they help tumor cells to tolerate chemotherapeutics and enable bacteria to become resistant to antibiotics.
Research in Bristol is led by Professors Mark Dillingham and Nigel Savery. This is one of two RepState projects available at the University of Bristol (see the description of another UOB project here) and will focus on newly discovered roles for the UvrD helicase in transcription-coupled nucleotide excision repair and R-loop homeostasis. We will use a wide range of complimentary biochemical, biophysical and structural approaches to investigate the mechanism of UvrD and the complexes it forms with other repair factors and RNA polymerase (for examples of previous work see the references).
Doctoral Training in RepState
Training incorporates a local program in Bristol, rotations within the European partner laboratories, and exposure to the non-academic sector through annual meetings. Fellows will follow scientific workshops, courses in transferable skills and career development, and will disseminate and communicate their projects to a diverse audience in collaboration with the creative sector. RepState fellows will form a new generation of innovative European scientists with a thorough understanding of fundamental quantitative principles underlying DNA repair biology, experience in technique development, career perspectives in multiple sectors and an understanding of the importance of the role of fundamental science for society and human health.
Professors Savery and Dillingham would be pleased to discuss this research project informally with interested candidates.
Eligibility
- Applicants should not have resided or performed their main activity (work, studies, etc) in the UK for more than 12 months in the 3 year period immediately prior to the start date of this position.
- Applicants should not have been awarded a doctorate and should have less than 4 years (full-time equivalent) research experience. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).
Position 3: PhD Student at Justus Liebig University Giessen, DE
Position 3: Function of the MutL state machine
In your studies you will aim to identify (1) steps requiring ATP hydrolysis, (2) conformational transitions in MutL controlling complex formation with protein and DNA (3) the role of ATPase asymmetry, and (4) the underlying molecular mechanism.
Job description
DNA mismatch repair is important for maintaining genome stability through repair of DNADNA mismatch repair is an essential process in reducing mutation frequency during DNA replication. Non-functional mismatch repair can result in a mutator phenotype and increase the risk of developing cancer in humans. This project is focused on the ATP-operated MutL state machine, which is the crossroad between mismatch recognition by MutS and coordination of the repair events by a variety of other factors. The successful candidate will elucidate the underlying molecular mechanisms of ATP hydrolysis by MutL. Dynamics of protein-DNA and protein-protein complex formation as well as conformational transitions in MutL will be obtained from MDS (with industrial partner Fluidic Analytics, UK), and fluorescence-based assays (FRET, PIFE) down to the single-molecule level (with French National Centre for Scientific Research, FR).
Work Environment
- Being part of the Doctoral Network RepState, a highly collaborative consortium consisting of 14 European participants coming from academia, industry and the creative sector
- An international, multidisciplinary training environment in fundamental life sciences and obtain insight into the role of basic chemical and physical principles underlying molecular steps in complex yet integrated molecular processes
- Training includes one or more rotations within European partner laboratories; excellent support during the doctoral thesis
- Collaboration with industry, to learn how technology development drives innovation in research
- Learn how to disseminate and communicate your project in close collaboration with the creative sector
- A diversified job with flexible working hours
- Opportunities to develop strong research skills and a solid academic profile
- Free use of local public transport (LandesTicket Hessen)
- More than 100 training seminars, workshops and e-learning opportunities per year for personal development, as well as a wide range of health and sports activities
- Remuneration according to TV-H, company pension scheme, child allowance and special payments
- Good compatibility of family and career (certificate “audit familiengerechte hochschule”)
Qualifications and skills
- Completed Master‘s or equivalent university degree in biology, biochemistry or a similar subject with a focus on molecular biology, biochemistry and/or biophysics
- Applicants should not have resided or performed their main activity (work, studies, etc) in Germany for more than 12 months in the 3 year period immediately prior to the start date of this position (mobility rule of the EU)
- Applicants for the positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate; this 4 year period is measured from the date of obtaining your MSc degree (or equivalent)
- Very good English language skills
Terms of employment
In accordance with § 611 BGB the position is to be filled on a fixed-term basis for 3 years as a full-time position in the H2020 / Marie Skłodowska-Curie Actions (https://marie-sklodowska-curie-actions.ec.europa.eu/) Doctoral Network RepState at the Chair of Biochemistry, Department of Biochemistry at the Faculty of Chemistry and Biology with the opportunity for own academic qualification.
Position 4: PhD Student at Leiden University Medical Center, NL
Unraveling the organization of the mismatch strand removal process
In your studies you will aim to reveal the molecular interaction between these different proteins during the strand removal process through biochemical and structural methods.
Job description
DNA mismatch repair is an essential process that removes mis-incorporated nucleotides that may be introduced during DNA replication. By doing so it reduces the mutation frequency of genome duplication by a 100 to 1000-fold. The removal of mismatched nucleotides requires the carefully orchestrated action of multiple proteins, including the mismatch repair proteins MutS, MutL and MutH, a DNA helicase and a DNA exonuclease. How these protein organize their sequential actions is poorly understood. The aim of this project is the reveal the molecular interaction between these different proteins during the strand removal process through biochemical and structural methods. Throughout the project you will be trained in diverse biochemical and biophysical techniques for protein purification and characterization and protein structure determination by cryo-electron microscopy.
Work Environment
This position is part of the Doctoral Training Network RepState, a highly collaborative consortium consisting of 14 European participants coming from academia, industry and the creative sector. You will be immersed in an international, multidisciplinary training environment in fundamental life sciences and obtain insight into the role of basic chemical and physical principles underlying molecular steps in complex yet integrated molecular processes. As the research relies on cutting-edge technologies, development of new approaches will be an integral part of your project. Training includes one or more rotations within European partner laboratories. Through collaboration with industry, you will learn how technology development drives innovation in research. In addition, you will learn how to disseminate and communicate your project in close collaboration with the creative sector.
The Leiden University Medical Center (LUMC) is a multi-disciplinary center for medical research located in the largest bioscience park in The Netherlands and has close collaborations with the Leiden University Faculty of Science. The LUMC is equipped with the latest instrumentation for biophysical characterization of proteins and as well as state-of-the-art cryo-electron microscopes including a Talos Arctica and two Titan Krios microscopes.
Qualifications and skills
We are looking for an enthusiastic candidate with a MSc in Biochemistry, Structural Biology or closely related field, good command of English (IELTS grade min. 6.5, or equivalent). We welcome applicants of all nationalities. Being able to present a certificate of good conduct is a condition for the appointment.
There are strict eligibility requirements for the PhD positions in MSCA-DN:
- Applicants should not have resided or performed their main activity (work, studies, etc) in the Netherlands for more than 12 months in the 3 year period immediately prior to the start date of this position.
- Applicants for the PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).
Position 5: PhD Student at Netherlands Cancer Insitute, NL
Structure and Function of the MutSα and MutLα state machines
In your studies you will aim to (1) define conditions that stabilize MutSα/MutLα complexes, (2) Solve cryo-EM structures of defined MutSα/MutLα states, (3) Use mutations to assess the effect of the ATPase cycle on activation of MutLα.
Job description
DNA mismatch repair is important for maintaining genome stability through repair of DNA replication errors. Non-functional mismatch repair results in a mutator phenotype and in humans increases the risk to develop cancer. Human mismatch repair starts when MutSα recognizes a mismatch and then requires MutLα to transmit this signal but also to help determine which strand to repair. Here we want to address how MutLα is activated by MutSα, PCNA and ATP.
You will use a combination of structural biology and quantitative biochemistry to study complex formation, conformational change and enzyme activity. You will be trained in protein purification and characterization, quantitative protein-protein analysis, enzyme assays and structural biology, particularly cryo-EM to study how MutLα is activated and during DNA mismatch repair.
Work Environment
This position is part of the Doctoral Training Network RepState, a highly collaborative consortium consisting of 14 European participants coming from academia, industry and the creative sector. You will be immersed in an international, multidisciplinary training environment in fundamental life sciences and obtain insight into the role of basic chemical and physical principles underlying molecular steps in complex yet integrated molecular processes. As the research relies on cutting-edge technologies, development of new approaches will be an integral part of your project. Training includes one or more rotations within European partner laboratories. Through collaboration with industry, you will learn how technology development drives innovation in research. In addition, you will learn how to disseminate and communicate your project in close collaboration with the creative sector.
The Netherlands Cancer Institute is an integrated cancer hospital and research institute. The NKI offers an international environment, where more than half of the ESR are from abroad and has an open and interactive culture. Our division is integrated with other structural biology groups (Tassos Perrakis, Robbie Joosten) as well as genetics groups and as a protein facility that has many international guests. We are well-equipped for protein biochemistry and structural biology, and for high-end cryo-EM we visit the nearby NeCEN facility.
Qualifications and skills
We are looking for an enthusiastic candidate with a MSc in Biochemistry, Structural Biology or closely related field, good command of English (IELTS grade min. 6.5, or equivalent). We welcome applicants of all nationalities. Being able to present a certificate of good conduct is a condition for the appointment.
There are strict eligibility requirements for the PhD positions in MSCA-DN:
- Applicants should not have resided or performed their main activity (work, studies, etc) in the Netherlands for more than 12 months in the 3 year period immediately prior to the start date of this position.
- Applicants for the PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).
Information and Application
For more information on the RepState training network, see www.repstate.eu. For more information about this position, please contact Titia Sixma (t.sixma@nki.nl).
Applications can be sent to - Dr. Katja Pechenizkaya (repstate@erasmusmc.nl) stating vacancy code NKI in the subject line.
Applications should include
- a cover letter explaining why you are interested in the project,
- resume,
- contact info for two referees, and
- detailed academic transcripts.
Position 6: PhD Student at University of Bristol, UK
Non-canonical roles for UvrD in DNA repair
In your studies you will develop novel bulk and single molecule assays to assess UvrD activity on RNA polymerase that is undergoing either normal transcription elongation, or elongation perturbed by DNA damage and/or the formation of toxic R-loops.
Applications are invited for a fully-funded 3-year PhD studentship starting in Autumn 2023 as part of the EU-wide doctoral training network RepState.
PhD Project Description
RepState is a highly collaborative and innovative doctoral training network consisting of 14 participants from academia, industry and the creative sector. It will train a new generation of scientists in biochemistry and biophysics to address central questions in biology concerning the mode of action of critical DNA Repair proteins. If left unchecked, unrepaired damage pre-disposes us to cancer and developmental defects. Accordingly, inherited or somatic mutations in DNA repair proteins are strongly associated with human disease including cancer. Moreover, DNA repair pathways are drug targets because they help tumor cells to tolerate chemotherapeutics and enable bacteria to become resistant to antibiotics.
Research in Bristol is led by Professors Mark Dillingham and Nigel Savery. This is one of two RepState projects available at the University of Bristol (see the description of another UOB project here) and will focus on newly discovered roles for the UvrD helicase in transcription-coupled nucleotide excision repair and R-loop homeostasis. We will use a wide range of complimentary biochemical, biophysical and structural approaches to investigate the mechanism of UvrD and the complexes it forms with other repair factors and RNA polymerase (for examples of previous work see the references).
Doctoral Training in RepState
Training incorporates a local program in Bristol, rotations within the European partner laboratories, and exposure to the non-academic sector through annual meetings. Fellows will follow scientific workshops, courses in transferable skills and career development, and will disseminate and communicate their projects to a diverse audience in collaboration with the creative sector. RepState fellows will form a new generation of innovative European scientists with a thorough understanding of fundamental quantitative principles underlying DNA repair biology, experience in technique development, career perspectives in multiple sectors and an understanding of the importance of the role of fundamental science for society and human health.
Professors Savery and Dillingham would be pleased to discuss this research project informally with interested candidates.
Eligibility
- Applicants should not have resided or performed their main activity (work, studies, etc) in the UK for more than 12 months in the 3 year period immediately prior to the start date of this position.
- Applicants should not have been awarded a doctorate and should have less than 4 years (full-time equivalent) research experience. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).
Position 7: PhD Student at University of Leeds, UK
Structural mass spectrometry for the analysis of nucleic-acid: protein interactions and applications in the study of DNA repair complexes
We will develop novel approaches for HDX-MS of oligonucleotides as well as chemical and photo-crosslinking of DNA-protein contacts and explore readouts of SHAPE analysis by advanced MS approaches, and develop hydroxyl radical footprinting for oligonucleotide higher-order structure determination.
Job description
DNA mismatch repair is important for maintaining genome stability through repair of DNA replication errors. Non-functional mismatch repair results in a mutator phenotype and in humans increases the risk to develop cancer. Human mismatch repair starts when MutSα recogni
This DR position is based in the University of Leeds and concerns the investigation of key protein complexes involved in DNA repair using structural MS. In particular, the project involves application of methods such as native MS, ion mobility, HDX-MS, covalent labelling approaches and chemical crosslinking to study conformations of DNA repair state machines such as the UvrD:RNAP and UvrD:MutL complexes. In addition, it will allow the researcher to pioneer new MS approaches to DNA structural biology. This project will be supervised by Prof Sobott, in collaboration with several other researchers across the network.
Work Environment
You will join the recently funded European Doctoral Network (DN) RepState: DNA Repair State Machines (https://www.repstate.eu/). RepState offers high-level doctoral training to 13 Doctoral Researchers (DRs) in six different countries. DRs will be supervised by researchers across the network, will be exposed to different sectors via planned placements, attend summer schools, and contribute to and organise workshops and conferences. You will be funded for 3 years and will pursue a doctoral degree during this time.
Qualifications and skills
Important eligibility rules for this position:
There are no restrictions on the nationality, but:
- Applicants must, at the time of recruitment, have not yet been awarded a doctorate degree and be in the first 4 years (full-time equivalent) of their research careers. This is measured from the date that you obtained the degree which would entitle you to embark on a PhD.
- At the time of recruitment, applicants must not have resided or carried out their main activity (work, studies, etc…) in the UK for more than 12 months in the 3 years immediately prior to their recruitment under the QSI project. Compulsory national service and/or short stays such as holidays are not taken into account.
Salary:
- The Marie Skłodowska-Curie Doctoral Researcher living allowance is fixed at £48,640.00 per annum including the mobility allowance (£53,119.35 if eligible for the family allowance). This figure is before employer’s and employee’s deductions for national insurance and taxes per year, which will be paid in Sterling using an appropriate conversion rate.
Information and Application
The position is filled
Position 8: PhD Student at CNRS, France
Single-molecule characterization of transcription-coupled DNA repair
We will focus on determining how the repair machinery successfully distinguishes the transcribed strand from the non-transcribed strand in the model bacterial system centered about the Mfd (“Mutation frequency decline”) protein and its downstream partners UvrA, UvrB, UvrC and UvrD.
Job description
Transcription-coupled repair (TCR) efficiently corrects bulky DNA lesions located on the coding strand of genes and plays an important protective role against ageing and cancer in humans. TCR begins when RNA polymerase (RNAP) becomes stalled on a lesion located on its transcribed strand and recruits downstream repair components to the lesion. Importantly, the process prioritizes repair of lesions on the transcribed strand over repair of other lesions simultaneously present on the non-transcribed strand. Your aim will be to determine how the repair machinery successfully distinguishes the transcribed strand from the non-transcribed strand in the model bacterial system centered about the Mfd (“Mutation frequency decline”) protein and its downstream partners UvrA, UvrB, UvrC and UvrD. For instance although UvrA and UvrB normally work together as a heterotetramer equally able to drive repair of both strands, structural considerations lead to a working hypothesis that a single UvrB is present in the TCR repair complex. To analyze the composition of repair complexes in real-time, you will use single-molecule approaches to enumerate protein components as repair reactions unfold. For this you will be offered training in biophysics, biochemistry, and molecular biology, and also benefit from the collaborative environment of the consortium by carrying out work on specific topics with partners in biochemistry of helicases (University of Bristol, UK) and microfluidics (Chalmers University of Technology, Sweden).
Work Environment
This position is hosted in the Repstate Doctoral Network’s “Molecular Motors and Machines” group located at the Institute of Biology of the Ecole Normale Supérieure in Paris, France. Our focus is the study of mechanistic processes underpinning gene transcription, replication and repair, observed in real-time and at single-molecule resolution. The group brings together biologists, physicists and chemists around the study of DNA repair mechanisms using a variety of single-molecule assays such as single-molecule nanomanipulation and single-molecule fluorescence to reconstruct and monitor in real-time complex multi-component multi-step reactions. This variety of cutting-edge tools and approaches provides a rich learning environment, supported by a dynamic consortium featuring a range of exciting opportunities for learning and networking including frequent meetings and training sessions, collaboration with industry and the creative sector, and one to two rotations in other Network groups.
The Institute of Biology of the Ecole Normale Supérieure is a diverse, fundamental research institute which provides a stimulating environment for graduate studies. The group is a part of the Functional Genomics section of the Institute, which covers fundamental processes of genome transcription, replication, repair, and evolution at scales that range from the molecular to the population.
Qualifications and skills
We are looking for an enthusiastic candidate with a MSc in Biochemistry, Biophysics, Structural Biology, or closely related field, good command of English (IELTS grade min. 6.5, or equivalent). We welcome applicants of all nationalities. Being able to present a certificate of good conduct is a condition for the appointment.
There are strict eligibility requirements for the PhD positions in MSCA-DN:
- Applicants should not have resided or performed their main activity (work, studies, etc) in France for more than 12 months in the 3 year period immediately prior to the start date of this position.
- Applicants for the PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).
Terms of employment
You will receive a temporary position for at least 3 years. The gross monthly salary is approximately € 2.750. In addition to benefits accorded under French labor laws, employment terms for Marie Curie projects (https://marie-sklodowska-curie-actions.ec.europa.eu/ ) apply for the first three years of employment.
Information and Application
The position is filled.
Information and Application
The position is filled.
Position 9: PhD Student at CNRS, France
Single-molecule characterization of DNA mismatch repair
The composition and stoichiometries of the MMR complex as it progresses through its pathway remains poorly understood. The composition of the incision complex containing MutH remains unclear, and your aim will be to determine the role and stoichiometry of the MutS and MutL components during this process
Job description
Mismatch repair (MMR) is essential to removal of replicative errors and its inherited deficiency in humans is associated with a variety of cancerous diseases such as hereditary non-polyposic colon cancer (HNPCC). MMR brings together a dynamic multi-components complex enacted in E. coli by the MutS, MutL and MutH proteins which respectively recognize a DNA mismatch, generate a complex with mismatch-activated MutS, and incise the mismatch-bearing strand. UvrD helicase then unwinds the incised strand to assist exonucleolytic degradation and set the stage for DNA re-synthesis. Although the roles of the protein components one by one are well-understood, the composition and stoichiometries of the MMR complex as it progresses through its pathway remains poorly understood. In particular, the composition of the incision complex containing MutH remains unclear, and your aim will be to determine the role and stoichiometry of the MutS and MutL components during this process. To analyze the composition of repair complexes in real-time, you will use single-molecule approaches to enumerate protein components as repair reactions unfold. For this you will be offered training in biophysics, biochemistry, and molecular biology, and also benefit from the collaborative environment of the consortium by carrying out work on specific topics with partners in biochemistry of mismatch repair (Erasmus MC, Netherlands), structural biology (Leiden University Medical Center, Netherlands), helicases (University of Bristol, UK) and microfluidics (Chalmers University of Technology, Sweden).
Work Environment
This position is hosted in the Repstate Doctoral Network’s “Molecular Motors and Machines” group located at the Institute of Biology of the Ecole Normale Supérieure in Paris, France. Our focus is the study of mechanistic processes underpinning gene transcription, replication and repair, observed in real-time and at single-molecule resolution. The group brings together biologists, physicists and chemists around the study of DNA repair mechanisms using a variety of single-molecule assays such as single-molecule nanomanipulation and single-molecule fluorescence to reconstruct and monitor in real-time complex multi-component multi-step reactions. This variety of cutting-edge tools and approaches provides a rich learning environment, supported by a dynamic consortium featuring a range of exciting opportunities for learning and networking including frequent meetings and training sessions, collaboration with industry and the creative sector, and one to two rotations in other Network groups.
The Institute of Biology of the Ecole Normale Supérieure is a diverse, fundamental research institute which provides a stimulating environment for graduate studies. The group is a part of the Functional Genomics section of the Institute, which covers fundamental processes of genome transcription, replication, repair, and evolution at scales that range from the molecular to the population.
Qualifications and skills
We are looking for an enthusiastic candidate with a MSc in Biochemistry, Biophysics, Structural Biology, or closely related field, good command of English (IELTS grade min. 6.5, or equivalent). We welcome applicants of all nationalities. Being able to present a certificate of good conduct is a condition for the appointment.
There are strict eligibility requirements for the PhD positions in MSCA-DN:
- Applicants should not have resided or performed their main activity (work, studies, etc) in French for more than 12 months in the 3 year period immediately prior to the start date of this position.
- Applicants for the PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).
Terms of employment
You will receive a temporary position for at least 3 years. The gross monthly salary is approximately € 2.750. In addition to benefits accorded under French labor laws, employment terms for Marie Curie projects (https://marie-sklodowska-curie-actions.ec.europa.eu/ ) apply for the first three years of employment.
Information and Application
The position is filled.
Job description
DNA mismatch repair is important for maintaining genome stability through repair of DNA replication errors. Non-functional mismatch repair results in a mutator phenotype and in humans increases the risk to develop cancer. Mismatch repair involves the coordinated action of multiple proteins, amongst which MutS and MutL (in prokaryotes) and MutSα and MutLα (in eukaryotes) that recognize the replication error. In this project you will study how the complete MMR reaction is coordinated by multiple state machines. Specifically, you will aim to find out how (1) the MutS/MutSα and MutL/MutLα ATPases coordinate repair and (2) how directionality is achieved. You will achieve this through using mutant and obligate asymmetric bacterial MMR repair proteins in our reconstituted E.coli MMR assay. You will purify human MMR proteins (with NKI, Amsterdam) and reconstitute the human MMR reaction so that analogies and differences with the bacterial system can be studied in detail. In collaboration with other consortium partners, you may then explore the actions of individual molecules on DNA in different reaction substeps using in vitro or in vivo single molecule approaches (CNRS Paris, Chalmers University Sweden, or Oxford University UK).
Work Environment
This position is part of the Doctoral Training Network RepState, a highly collaborative consortium consisting of 14 European participants coming from academia, industry and the creative sector. You will be immersed in an international, multidisciplinary training environment in fundamental life sciences and obtain insight into the role of basic chemical and physical principles underlying molecular steps in complex yet integrated molecular processes. As the research relies on cutting-edge technologies, development of new approaches will be an integral part of your project. Training includes one or more rotations within European partner laboratories. Through collaboration with industry, you will learn how technology development drives innovation in research. In addition, you will learn how to disseminate and communicate your project in close collaboration with the creative sector.
Erasmus MC is the largest academic hospital in The Netherlands and strives towards a healthy population and excellence in healthcare through research and education. The Department of Molecular Genetics is well known within the field of DNA repair for its competitive international research which spans the experimental range from animal models to single molecule imaging. Our research group focuses on biochemical and enzymatic approaches to understand the mechanisms of complex genome transactions such as DNA mismatch repair and the regulation of homeologous recombination at the molecular level.
Qualifications and skills
We are looking for an enthusiastic candidate with a MSc in Biochemistry, Structural Biology or closely related field, good command of English (IELTS grade min. 6.5, or equivalent). We welcome applicants of all nationalities. Being able to present a certificate of good conduct is a condition for the appointment.
There are strict eligibility requirements for the PhD positions in MSCA-DN:
- Applicants should not have resided or performed their main activity (work, studies, etc) in the Netherlands for more than 12 months in the 3 year period immediately prior to the start date of this position.
- Applicants for the PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).
Terms of employment
You will receive a temporary position for 4 years. The gross monthly salary is € 2.789,-in the 1st year and increases to € 3.536,- in the 4th year (scale OIO). The terms of employment are according to the Collective Bargaining Agreement for Dutch University Medical Centers (CAO UMC). Additionally, employment terms for Marie Curie projects (https://marie-sklodowska-curie-actions.ec.europa.eu/ ) apply for the first three years of employment.
Position 11: PhD Student at UEF, Finland
Structural mass spectrometry for the analysis of protein:protein complex formation and conformational changes in DNA repair proteins
We aim to determine the stoichiometries, interactions and interfaces of these complexes, as well as their conformational spectra, ligand interactions and how these change in different nucleotide-bound states.
Job description
DNA mismatch repair is important for maintaining genome stability through repair of DNA replication errors. Non-functional mismatch repair results in a mutator phenotype and in humans increases the risk to develop cancer. In this research project, structure and composition of DNA mismatch repair (MMR) and transcription-coupled nucleotide-excision repair (TC-NER) protein components using state-of-the-art high-resolution mass spectrometry (HRMS) techniques (i.e., native FT-ICR and time-of-flight MS, ion mobility MS, and structure-sensitive native top-down fragmentation). We aim at determining complex stoichiometries, interaction strength and interfaces of these complexes, as well as their conformational changes, ligand interactions and how these affect different nucleotide-bound states.
Work Environment
This position is part of the Doctoral Training Network RepState, a highly collaborative consortium consisting of 14 European participants coming from academia, industry, and the creative sector. You will be immersed in an international, multidisciplinary training environment in fundamental life sciences and obtain insight into the role of basic chemical and physical principles underlying molecular steps in complex yet integrated molecular processes. As the research relies on cutting-edge technologies, development of new approaches will be an integral part of your project. Training includes one or more rotations within European partner laboratories. Through collaboration with industry, you will learn how technology development drives innovation in research. In addition, you will learn how to disseminate and communicate your project in close collaboration with the creative sector.
The University of Eastern Finland is the most multidisciplinary university in Finland, comprising four faculties in two campuses located in Joensuu and Kuopio. UEF Department of Chemistry belongs to the Faculty of Science, Forestry and Technology and is a highly research chemist education-oriented chemistry department in Finland. The Bioorganic Chemistry research group (led by profs. Janne Jänis and Juha Rouvinen) at UEF Chemistry has over 30 years of experience in developing mass spectrometry for structural biology research. The department is well equipped with three state-of-the-art HRMS instruments, including Finland’s only FT-ICR system.
The lab is also a technology platform of Biocenter Finland and provides services in Europe via Instruct-ERIC as part of the national FINStruct network.
Qualifications and skills
We are looking for an enthusiastic candidate with a MSc in Biochemistry, Structural Biology or closely related field, good command of English (IELTS grade min. 6.5, or equivalent). We welcome applicants of all nationalities. Being able to present a certificate of good conduct is a condition for the appointment.
There are strict eligibility requirements for the PhD positions in MSCA-DN:
- Applicants should not have resided or performed their main activity (work, studies, etc) in Finland for more than 12 months in the 3 year period immediately prior to the start date of this position.
- Applicants for the PhD positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate. This 4 year period is measured from the date of obtaining your MSc degree (or equivalent).
Terms of employment
You will receive a temporary position for 4 years. The terms of employment are according to the General Collective Agreement for Finnish Universities.
Salary
Your salary will be according to the salary system of EU MSCA DN networks with correction to Finland coefficient.
Information and Application
The position is filled.
Position 12: PhD Student at Chalmers University of Technology, Sweden
Diffusion of MMR-proteins along nanoconfined DNA
We will reconstitute DNA mismatch repair in a nanofluidic set up that allows monitoring of the binding and movement of labelled repair proteins on specific DNA molecules that are confined in nanofluidic channels.
Information about the project
The research in this specific PhD project is related to studying DNA-mismatch repair using single molecule methods, in particular nanofluidics and fluorescence microscopy. We will analyse how proteins that repair DNA mismatches bind to DNA, find their target, diffuse along DNA and interact with other proteins to complete the repair process. The student will enjoy at least one longer research visit in an academic or industrial partner.
In the Westerlund “BioNanoFluidics” group we use nanofluidic devices to study biomolecules in general and DNA in particular. Our projects range from fundamental biophysics of DNA-protein interactions to analysis of clinical DNA, for example diagnostics of antibiotic resistance.
The Chemical biology division is the home of seven research groups. We combine and develop protein engineering, synthetic chemistry, and state-of-the-art biophysical methods (spectroscopy, live cell imaging and nanotechnology to address cutting-edge questions in biology to meet medical challenges related to human health. Our joint expertise is strategic and spans from molecular biophysics of single molecules to cell and organism biology.
Major responsibilities
You will work in your own research project, but be part of a larger research team in the Westerlund group that develop and use single DNA molecule techniques. You will also take part in mandatory and elective program in the training network and in the local research school (total 60ECTS required).
Supervision of master and bachelor theses, as well as teaching on the bachelor and master level can also be part of the training.
Qualifications
There are strict eligibility requirements for the PhD positions in MSCA*DN. Please, read the requirements.
To qualify for this position you must have a registered master’s level degree corresponding to at least 240 higher education credits in biochemistry, biophysics or similar. Experience in DNA analysis, data analysis using Matlab or R, molecular biology, fluorescence microscopy, optical tweezers and nanofluidics is meritious.
Contract terms
Full-time temporary employment. The position is limited to a maximum of five years.
We offer
Chalmers offers a cultivating and inspiring working environment in the coastal city of Gothenburg. Read more about working at Chalmers and our benefits for employees. Chalmers aims to actively improve our gender balance. We work broadly with equality projects, for example the GENIE Initiative on gender equality for excellence. Equality and diversity are substantial foundations in all activities at Chalmers.
Position 13: PhD Student at JLU, Germany
Dissection and controlling the UvrD state machine
We aim to identify (1) steps and structural changes required in UvrD and the DNA substrates, (2) determine key conformational states and their transitions in UvrD which might be controlled by interaction partners, and (3) control the conformational states in UvrD using permanent or transient (caged/photo switchable) crosslinks and/or protein complex formation.
indicate reference number 268/08 while applying
Job description
DNA mismatch repair is an essential process in reducing mutation frequency during DNA replication. Non-functional mismatch repair can result in a mutator phenotype and increase the risk of developing cancer in humans. A key step in mismatch repair is the removal of the erroneous strand by the helicase UvrD- This project is focused on how UvrD is loaded onto the DNA, and how this is related to the conformational transition in UvrD for coordinating the timing of unwinding and its directionality. We aim to identify (1) steps and structural changes required in UvrD and the DNA substrates, (2) determine key conformational states and their transitions in UvrD which might be controlled by interaction partners, and (3) control the conformational states in UvrD using permanent or transient (caged/photo switchable) crosslinks and/or protein complex formation. Dynamics of protein-DNA and protein-protein complex formation as well as conformational transitions in UvrD will be obtained from fluorescence-based assays (FRET, PIFE) down to the single-molecule level (with French National Centre for Scientific Research, FR and Chalmers University of Technology, SE). Relevant states of UvrD and UvrD with DNA will be trapped for functional and structural assays (HDX-MS with University of Leeds, UK and University of Central Finland)
Work Environment
- Being part of the Doctoral Network RepState, a highly collaborative consortium consisting of 14 European participants coming from academia, industry and the creative sector
- An international, multidisciplinary training environment in fundamental life sciences and obtain insight into the role of basic chemical and physical principles underlying molecular steps in complex yet integrated molecular processes
- Training includes one or more rotations within European partner laboratories; excellent support during the doctoral thesis
- Collaboration with industry, to learn how technology development drives innovation in research
- Learn how to disseminate and communicate your project in close collaboration with the creative sector
- A diversified job with flexible working hours
- Opportunities to develop strong research skills and a solid academic profile
- Free use of local public transport (LandesTicket Hessen)
- More than 100 training seminars, workshops and e-learning opportunities per year for personal development, as well as a wide range of health and sports activities
- Remuneration according to TV-H, company pension scheme, child allowance and special payments
- Good compatibility of family and career (certificate “audit familiengerechte hochschule”)
Qualifications and skills
- Completed Master‘s or equivalent university degree in biology, biochemistry or a similar subject with a focus on molecular biology, biochemistry and/or biophysics
- Applicants should not have resided or performed their main activity (work, studies, etc) in Germany for more than 12 months in the 3 year period immediately prior to the start date of this position (mobility rule of the EU)
- Applicants for the positions should be in the first 4 years (full-time equivalent) of their research careers and not yet have been awarded a doctorate; this 4 year period is measured from the date of obtaining your MSc degree (or equivalent)
- Very good English language skills
Terms of employment
In accordance with § 611 BGB the position is to be filled on a fixed-term basis for 3 years as a full-time position in the H2020 / Marie Skłodowska-Curie Actions (https://marie-sklodowska-curie-actions.ec.europa.eu/) Doctoral Network RepState at the Chair of Biochemistry, Department of Biochemistry at the Faculty of Chemistry and Biology with the opportunity for own academic qualification.
Information and Application
The position is filled.